Nocturnal hypoglycemia often remains unrecognized (1). Detection and prevention of such events is, however, important: repeated nocturnal hypoglycemia might compromise daytime performance and counterregulation (2).

Hypoglycemia incidence has been reported to be much higher in children than in adults (3). Therefore, identification of nocturnal hypoglycemia is of special importance in clinical pediatric diabetology.

The aim of this study was to evaluate the frequency and duration of nocturnal hypoglycemia in children with diabetes and to identify risk factors for such events. As hypoglycemia is associated with exercise, the influence of physical activity was studied by combining glucose measurements with accelerometry.

A total of 60 children with type 1 diabetes for >6 months were included, and data from 51 subjects (29 male, 22 female; aged 2–17 years; HbA1c 8.1 ± 1.5% [65.4 ± 16.4 mmol/mol]) were complete. A total of 36 subjects received multiple injection therapy (MIT), and 15 subjects were on continuous subcutaneous insulin infusion (CSII). The insulin types used were aspart and detemir in most of the patients. For 6 days, continuous glucose monitoring was performed (Medtronic iPro), and physical activity was recorded by accelerometry. Patients noted sleep time and symptoms of hypoglycemia. Nocturnal hypoglycemia was defined as a glucose level <3.7 mmol/L during nighttime. Moderate-to-vigorous physical activity (MVPA) was defined as ≥2,296 counts per min and vigorous physical activity (VPA) as ≥4,012 counts per min based on published cutoffs (4).

Overall, 128 episodes of nocturnal hypoglycemia were found, only 8 of which were symptomatic. There were 97 nights (32.7%) in which one or more episodes of hypoglycemia occurred. Hypoglycemia duration ranged from 10 to 665 min: 36% of the episodes lasted <1 h, 34% 1–3 h, 24% 3–6 h, and 6% >6 h.

Daytime physical activity was associated with the occurrence of nocturnal hypoglycemia: 1 h of MVPA increased the risk of nocturnal hypoglycemia by 58% (P = 0.009) and 1 h of VPA by 82% (P = 0.01). The risk of nocturnal hypoglycemia was increased 2.5-fold when bedtime glucose was <6 mmol/L (P < 0.001) (Fig. 1). Hypoglycemia frequency was negatively correlated to HbA1c (−0.32, P = 0.022). Nocturnal hypoglycemia was not associated with age, insulin dosage, treatment type (MIT vs. CSII), or diabetes duration.

Figure 1

Risk of nocturnal hypoglycemia correlated to bedtime glucose.

Figure 1

Risk of nocturnal hypoglycemia correlated to bedtime glucose.

Close modal

Our data reveal that in children with diabetes, nocturnal hypoglycemia is very frequent, mostly asymptomatic, and often prolonged for hours. Two strong risk factors, low bedtime glucose and daytime physical activity, could be identified.

Even short periods of intensive physical activity led to prolonged asymptomatic nocturnal hypoglycemia. With every increase of 60 min of activity, there is a 60–80% higher risk of hypoglycemia. A recent study in a smaller cohort of 19 adolescents with diabetes also combining accelerometry and continuous glucose monitoring found similar results (5), although these patients were older (aged 14–20 years) and more active (117 min/day of MVPA vs. 55 min/day). Children with diabetes should be encouraged to participate in sports, but they must be trained how to prevent hypoglycemia. As bedtime glucose <6 mmol/L more than doubles the risk of nocturnal hypoglycemia, it should be mandatory to instruct patients to increase carbohydrate intake, adapt insulin dosage, and retest blood glucose during the night, especially after exercise.

Acknowledgments. The authors thank the participating children and their families for their interest in the study and their collaboration and diabetes nurse Vreni Ritschard (University Children's Hospital Basel) for her support.

Funding. This study was partially supported by research grants from the University of Basel and the Basel Diabetes Association. Medtronic provided 4 iPro and Enlite Sensors.

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Author Contributions. S.B. designed and ran the study and wrote the manuscript. M.H. contributed to patient recruitment and reviewed and edited the manuscript. E.M.-D. provided accelerometers and analyzed accelerometer data. K.D. performed the statistical analysis and reviewed the manuscript. U.Z. contributed to the discussion and reviewed and edited the manuscript. S.B. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Prior Presentation. Preliminary results of this study were presented orally at the Annual Congress of the Swiss Society of Paediatrics, Basel, Switzerland, 12–13 June 2014 and the Annual Meeting of the Swiss Society of Endocrinology and Diabetology, Bern, Switzerland, 27–28 November 2014. Data were shown in poster form at the 53rd Annual Meeting of the European Society of Pediatric Endocrinology, Dublin, Ireland, 18–20 September 2014.

1.
Amin
R
,
Ross
K
,
Acerini
CL
,
Edge
JA
,
Warner
J
,
Dunger
DB
.
Hypoglycemia prevalence in prepubertal children with type 1 diabetes on standard insulin regimen: use of continuous glucose monitoring system
.
Diabetes Care
2003
;
26
:
662
667
2.
Veneman
T
,
Mitrakou
A
,
Mokan
M
,
Cryer
P
,
Gerich
J
.
Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia
.
Diabetes
1993
;
42
:
1233
1237
3.
Davis
EA
,
Keating
B
,
Byrne
GC
,
Russell
M
,
Jones
TW
.
Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus
.
Arch Dis Child
1998
;
78
:
111
115
4.
Evenson
KR
,
Catellier
DJ
,
Gill
K
,
Ondrak
KS
,
McMurray
RG
.
Calibration of two objective measures of physical activity for children
.
J Sports Sci
2008
;
26
:
1557
1565
5.
Metcalf
KM
,
Singhvi
A
,
Tsalikian
E
, et al
.
Effects of moderate-to-vigorous intensity physical activity on overnight and next-day hypoglycemia in active adolescents with type 1 diabetes
.
Diabetes Care
2014
;
37
:
1272
1278